PDF(Pubmed)
Abstract：
Melanin is produced by melanocytes to protect human skin from harmful ultraviolet radiation. During skin cell renewal, melanin and dead skin cells are disposed of. However, prolonged exposure to ultraviolet rays or aging can disturb this cycle, leading to skin hyperpigmentation due to melanin accumulation. Tyrosinase is a crucial enzyme involved in melanin biosynthesis. Although various compounds, including tyrosine inhibitors, that counteract melanin accumulation have been reported, some, such as hydroquinone, are toxic and can cause vitiligo. Meanwhile, the skin is the largest organ and the outermost layer of the immune system, containing a diverse range of bacteria that produce low-toxicity compounds. In the current study, we aim to identify metabolites produced by skin microbiota that inhibit tyrosinase. Specifically, mushroom tyrosinase served as the study model. Following commensal skin bacteria screening, Corynebacterium tuberculostearicum was found to inhibit tyrosinase activity. The active compound was cyclo(l-Pro-l-Tyr); commercially available cyclo(l-Pro-l-Tyr) also exhibited inhibitory activity. Docking simulations suggested that cyclo(l-Pro-l-Tyr) binds to the substrate-binding site of mushroom tyrosinase, obstructing the substrate pocket and preventing its activity. Hence, cyclo(l-Pro-l-Tyr) might have potential applications as a cosmetic agent and food additive.
摘要：
黑色素由黑素细胞产生，以保护人类皮肤免受有害的紫外线辐射。在皮肤细胞更新期间，黑色素和死皮细胞被处理掉。然而,长时间暴露于紫外线或老化会扰乱这个周期，由于黑色素积累导致皮肤色素沉着过度。酪氨酸酶是参与黑色素生物合成的关键酶。虽然各种化合物，包括酪氨酸抑制剂,据报道，可以抵消黑色素的积累，一些,如对苯二酚，是有毒的，会导致白癜风。同时,皮肤是最大的器官，也是免疫系统的最外层，含有多种产生低毒性化合物的细菌。在目前的研究中,我们的目标是确定抑制酪氨酸酶的皮肤微生物群产生的代谢产物。具体来说,蘑菇酪氨酸酶作为研究模型。经过共生皮肤细菌筛查，发现结核杆菌抑制酪氨酸酶活性。活性化合物是环(l-Pro-l-Tyr);市售的环(l-Pro-l-Tyr)也表现出抑制活性。对接模拟表明，环（l-Pro-l-Tyr）与蘑菇酪氨酸酶的底物结合位点结合，阻碍基材袋并阻止其活动。因此，cyclo（l-Pro-l-Tyr）可能具有作为化妆品和食品添加剂的潜在应用。
